Nitroimidazoles Part 8. Synthesis and Anti-HIV Activity of New 4-Nitroimidazole Derivatives Using the Suzuki Cross-Coupling Reaction

Abstract

The development of new HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating structures of increased potency. To this end, a series of 1-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-4-(1,1 -biaryl)-4-yl-piperazine derivatives (6a-l) was synthesized via the Suzuki coupling reaction. Analogously, coupling of the acid derivative 5, prepared from 4, with various amino acid methyl esters in the presence of HOBt/DCC reagents afforded the benzamide derivatives 8-11. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All compounds are inactive, except compound 6f which showed inhibition of HIV-1 with EC 50 = 2.60 µg mL −1 with a selectivity index (SI) of 9.

Novel hybrid motifs of 4-nitroimidazole-piperazinyl tagged 1,2,3-triazoles: Synthesis, crystal structure, anticancer evaluations, and molecular docking study

“…The benzylation of the commercially available 4-nitroimidazoles 1 is carried out with benzyl chloride to produce compound 2 [ 87 ]. The bromination of N 1-benzyl-2- methyl-4-nitroimidazole 2 , with liquid bromine in dimethylformamide (DMF) in the presence of potassium carbonate as a base has afforded the desired product 3 [ 88 ]. The reaction of 5-bromo- N 1- benzyl-2-methyl-4- nitroimidazole 3 with piperazine using isopropanol as a solvent gives compound 4 [ 88 ].…”

“…The bromination of N 1-benzyl-2- methyl-4-nitroimidazole 2 , with liquid bromine in dimethylformamide (DMF) in the presence of potassium carbonate as a base has afforded the desired product 3 [ 88 ]. The reaction of 5-bromo- N 1- benzyl-2-methyl-4- nitroimidazole 3 with piperazine using isopropanol as a solvent gives compound 4 [ 88 ]. The major scaffold 5 is prepared by the reaction of the piperazine derivative 4 with propargyl bromide using NaH [ 89 ] as yellow flakes with 82% yield ( Scheme 1 ).…”

Suzuki - Miyaura Cross-Coupling Of Cetirizine Impurity A : Synthesis, Charactrization, Molecular Docking And Antioxidant Activity

“…Also, the spectrum of ( 13 C-NMR) showed signal at frequency signals at δ=53.18 due to methyl group and the single at δ = 44.22 ,53.15 ppm that belong to the carbons of Piperazine ring, , also show frequency signal at δ= 74.00 ppm of due to methyne group (charial center C-5), as well as show single in δ=107.41 -142.42 ppm due to carbone of aromatic rings and also single at δ= 158.97 ppm to carbon associated with fluoro group (C-17). The FT-IR spectrum of (8) in Figure (3)(4)(5)(6)(7)(8)(9)(10) showed the appearance of the band at the frequencies (3390 cm -1 ) to the group (N-H) and disappearance chloride group. The spectrum of ( 1 H-NMR) showed the single at δ =2.30 ppm refer to amine group (H-9), and also show δ= 3.39, 3.47 ppm belonging to the protons of Piprazine ring, displacement at δ= 4.30 due to chiral center (methyne group) (H-5), displacements at δ = 7.18-8.73 (m, H-ar.)…”

Synthesis, anticancer activity and molecular docking studies of new 4-nitroimidazole derivatives

“…Based on the imidazole pharmacological importance of imidazole derivatives and in contituation of our previous work on imidazole analogues with their antiviral and anticancer activity, [22][23][24][25][26][27][28][29] we report here new derivatives of nitroimidazole-containing piperazine derivatives and evaluation of their anticancer activity as well as the molecular docking study.…”